The proposed study would examine the relationships between hormonal factors, inflammatory mediators, related gene variants and adult-onset asthma in the Nurses' Health Study (NHS). The NHS is an ongoing prospective cohort study involving 121,700 women age 30 to 55 in 1976. Since 1988, all participants have been asked about a new "physician diagnosis of asthma" and a new "physician diagnosis of chronic obstructive pulmonary disease (COPD)." The primary aim will be to examine the relationship of endogenous female reproductive hormones and risk of newly diagnosed asthma. The main hypotheses are listed here as questions: 1) Do elevated endogenous levels of free (bioavailable) estradiol and other estrogens prospectively increase risk of physician diagnosed asthma in postmenopausal women? 2) Do elevated estrogen-associated inflammatory markers, such as C-reactive protein and interleukin-6, prospectively predict adult-onset asthma? 3) Do estrogen receptor and metabolism gene variants, such as the low activity allele of catechol-O-methyl transferase (COMT), increase risk of adult-onset asthma among postmenopausal women? We propose to study the above hypotheses in nested case-control studies in the cohort of postmenopausal women in the NHS. In 1989, 23,099 blood samples were obtained from postmenopausal women. Follow-up of these participants through 2000 revealed approximately 300 reports of new physician diagnoses of diagnosed asthma that required use of an asthma medication. Use of this existing cohort with previously collected blood samples will provide relatively quick and very cost-effective answers to longstanding uncertainty about the effect of female reproductive hormones on asthma.